Biodegradable block copolymers with modifiable surface

Abstract

A block copolymer containing a) a hydrophobic biodegradable polymer, b) a hydrophilic polymer and c) at least one reactive group for covalent binding of a surface-modifying substance d) to the hydrophilic polymer b) is disclosed. Shaped bodies are formed to consist of the block copolymer and are utilized as carriers for tissue culture and active substances and for controlled release and targeted administration of active substances.

Description

CROSS-REFERENCE[0001]This application is a continuation of U.S. application Ser. No. 10 / 019,797, filed Jul. 26, 2002, the entire contents of which are hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]1. Field of the Invention[0003]The disclosure relates to block copolymers with a hydrophobic biodegradable component and a hydrophilic biocompatible component, which permit the selective binding of surface-modifying substances and at the same time can suppress the non-selective adhesion of unwanted substances, and to shaped bodies produced therefrom.[0004]Such block copolymers are particularly suitable as carriers for cells for tissue culture, as carriers for active substances such as medications, in particular for controlled release (drug delivery system) and for targeted administration of active substances (drug targeting).[0005]2. Description of Related Art[0006]Biomaterials, which include the block copolymers according to the disclosure, play a dominant role in a ra...

AI Technical Summary

Benefits of technology

The patent text describes a need for biodegradable polymers that have specific properties such as masking the surface to prevent adsorption of substances, suppression of cell adhesion, and the ability to be coated with various surface-modifying substances. The text describes a block copolymer that meets these requirements and can be used for drug delivery, tissue engineering, and other applications. The block copolymer has a unique structure that allows for easy modification and the ability to leave the body after implantation. The properties of the block copolymer can be fixed by the selection of components.

Problems solved by technology

A disadvantage of many biomaterials, which are only used temporarily in the body, such as pins or plates in the surgical field, for example, is that they have to be removed after application.

A particular characteristic of these polymers is their low solubility in aqueous media, which only improves through polymer chain degradation, i.e. hydrolysis to lower-molecular oligomers or monomers, and thus leads to erosion of these materials.

This can result in the biodegradable medicinal agent carrier not releasing its dosage to the desired extent and not with the desired kinetics.

In an extreme case, this can also lead to inactivation of the active substance.

The adsorption of active substances is therefore undesirable in many cases and must be suppressed.

The surface properties of biodegradable polymers also play an important role in the field of tissue engineering:

1. The interactions between cells and polymer determine cell growth and cell differentiation. Natural anchorage mechanisms of the cells are responsible for adhesion of the cells to the polymer surfaces. Proteins such as integrins, for example, allow cells to adhere to specific amino acid sequences. The adhesion to biodegradable polymers occurs as a result of proteins from body fluids or cell culture media adsorbing non-specifically to the polymer surfaces and, in turn, the cells themselves adhering to the corresponding amino acid sequences of the proteins. This non-specific adsorption of proteins causes a plurality of different cells to adhere to the surface. This is above all disadvantageous if a specific cell type is to be adhered to the biodegradable polymer. It is therefore desirable to examine the adsorption of proteins and peptides.

2. The amino acid sequences to which cells adhere are often specific for a cell type, i.e. if the surface of a polymer is coated with a cell-specific sequence, then this cell type preferably adheres.

3. The membrane of a cell carries a series of receptors, in which case the behavior of the cell can be influenced via these receptors. Therefore, if corresponding “signal substances” such as hormones, growth factors or cytokines, for example, are located on the surface of polymers, to which the receptors can bind, the behavior of the cells adhering thereto via the receptors may be influenced via these correspondingly coated polymer surfaces.

A disadvantage of these polymers is that the functional groups, in this case amino groups, are only accessed in the surface with difficulty.

A disadvantage is that the non-specific adsorption of unwanted proteins and peptides occurs in the polymer obtained.

However, a disadvantage is that by anchoring avidin, a protein is used which is exogenous and can therefore lead to undesirable reactions.

In addition, the substance to be anchored must first be biotinyled, which complicates the process and thus restricts applicability.

At the same time, the surface is coated with avidin, which is undesirable for many applications.

This is an additional process step and undesirably increases the expense for application of this process.

The process assumes the existence of functional groups and is not suitable for the suppression of non-specific adsorption.

The process has the same disadvantages as described in U.S. Pat. No. 5,330,911 and assumes the existence of corresponding functional groups on the polymer surface.

The resulting disadvantage here is also that no adequate masking of the surface is achieved and non-specific adsorption cannot be suppressed.

The disadvantage of the process is again that the adsorption of undesirable substances is not suppressed by this structure.

U.S. Pat. No. 5,320,840 describes a polymer which is water-soluble and does not therefore meet the requirements for a solid water-insoluble biodegradable matrix.

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